We shall attempt to discriminate gene carriers from non-gene carriers in the Cancer Family Syndrome (four families) and in a family with hereditary site specific colon cancer on the basis of: (1) thymidine labeling of colonic epithelium; (2) growth characteristics of colonic epithelium cultured in vitro; (3) tetraploidy in cutaneous epithelium; (4) growth characteristics and viral transformation of cutaneous fibroblasts; (5) recognitive immunity in mixed lymphocyte culture; and (6) fecal cholesterol degradation products. These putative biomarkers of cancer susceptibility will be subjected to a biostatistical-genetic analysis utilizing maximum likelihood techniques in search for the marker or complex of markers most closely associated with cancer risk status in patients from these families. We will also perform a genetic linkage analysis to determine if variation in these quantitative markers can be shown to be associated chromosomally with classical genetic markers. All statistical methods will be directed towards a substantive verification of the basic cancer genetics model proposed for these families and the usefulness of a biomarker index for identification of gene carriers. Recognition of markers specific to the cancer prone genotype will have important implications for identification of high risk patients in the general asymptomatic population and will be of utility in the study of mechanisms of carcinogenesis.